| First Author | Nakamura F | Year | 2017 |
| Journal | J Neurosci | Volume | 37 |
| Issue | 30 | Pages | 7125-7139 |
| PubMed ID | 28637841 | Mgi Jnum | J:244898 |
| Mgi Id | MGI:5913677 | Doi | 10.1523/JNEUROSCI.2519-16.2017 |
| Citation | Nakamura F, et al. (2017) Protein Tyrosine Phosphatase delta Mediates the Sema3A-Induced Cortical Basal Dendritic Arborization through the Activation of Fyn Tyrosine Kinase. J Neurosci 37(30):7125-7139 |
| abstractText | Leukocyte common antigen-related (LAR) class protein tyrosine phosphatases (PTPs) are critical for axonal guidance; however, their relation to specific guidance cues is poorly defined. We here show that PTP-3, a LAR homolog in Caenorhabditis elegans, is involved in axon guidance regulated by Semaphorin-2A-signaling. PTPdelta, one of the vertebrate LAR class PTPs, participates in the Semaphorin-3A (Sema3A)-induced growth cone collapse response of primary cultured dorsal root ganglion neurons from Mus musculus embryos. In vivo, however, the contribution of PTPdelta in Sema3A-regualted axon guidance was minimal. Instead, PTPdelta played a major role in Sema3A-dependent cortical dendritic growth. Ptpdelta-/- and Sema3a-/- mutant mice exhibited poor arborization of basal dendrites of cortical layer V neurons. This phenotype was observed in both male and female mutants. The double-heterozygous mutants, Ptpdelta+/-; Sema3a+/-, also showed a similar phenotype, indicating the genetic interaction. In Ptpdelta-/- brains, Fyn and Src kinases were hyperphosphorylated at their C-terminal Tyr527 residues. Sema3A-stimulation induced dephosphorylation of Tyr527 in the dendrites of wild-type cortical neurons but not of Ptpdelta-/- Arborization of cortical basal dendrites was reduced in Fyn-/- as well as in Ptpdelta+/-; Fyn+/- double-heterozygous mutants. Collectively, PTPdelta mediates Sema3A-signaling through the activation of Fyn by C-terminal dephosphorylation.SIGNIFICANCE STATEMENT The relation of leukocyte common antigen-related (LAR) class protein tyrosine phosphatases (PTPs) and specific axon guidance cues is poorly defined. We show that PTP-3, a LAR homolog in Caenorhabditis elegans, participates in Sema2A-regulated axon guidance. PTPdelta, a member of vertebrate LAR class PTPs, is involved in Sema3A-regulated cortical dendritic growth. In Sema3A signaling, PTPdelta activates Fyn and Src kinases by dephosphorylating their C-terminal Tyr residues. This is the first evidence showing that LAR class PTPs participate in Semaphorin signaling in vivo. |
